Both ethyl alcohol and morphine have central nervous system (CNS) cholinergic and adrenergic effects, and both drugs can produce physical dependence and tolerance with abrupt removal of the drug leading to the withdrawal syndrome. The benzodiazepines, which possess some cholinergic and adrenergic effects, have been used clinically to combat withdrawal effects from alcohol. Tolerance and physical dependence are postulated to be associated with changes in receptor sensitivity. Cholinergic receptor activity is thought to be mediated by guanosine 3',5'-monophosphate. The opiate receptor and the Beta adrenergic receptor appear to be closely related in the mouse. The Beta adrenergic receptor is thought to be an adenylate cyclase, hence adenosine 3',5'-monophosphate may be mediating opiate receptor activity as well as adrenergic receptor activity. We propose, therefore, to examine some effects of ethyl alcohol, morphine, and the benzodiazepines at the CNS receptor level in the mouse with particular emphasis on the mediation of the consequent receptor activity by guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate. Nicotinic and muscarinic cholinergic activity and opiate receptor activity will especially be studied during the development of dependence on, and withdrawal from ethanol and morphine. Changes in cholinergic and receptor sensitivites during the development of drug dependence and during withdrawal syndrome will be correlated with alterations in cyclic nucleotide levels and changes in adenylate, and guanylate, cyclase and phosphodiesterase activities. The neurochemical effect of the benzodiazepines on the previously described systems will be studied during ethanol withdrawal.